Transformer-based Multi-label Deep Learning Model is Efficient for Detecting Ankle Lateral and Medial Ligament Injuries on MRI and Improving Clinicians' Diagnostic Accuracy for Rotational Chronic Ankle Instability.

PURPOSE: To develop a deep learning (DL) model that can simultaneously detect lateral and medial collateral ligament injuries of the ankle, aiding in the diagnosis of chronic ankle instability (CAI), and assess its impact on clinicians' diagnostic performance. METHODS: DL models were developed and external validated on retrospectively collected ankle MRIs between April 2016 and March 2022 respectively at three centers. Included patients were confirmed diagnoses of CAI through arthroscopy, as well as individuals who had undergone MRI and physical examinations that ruled out ligament injuries. DL models were constructed based on a multi-label paradigm. A transformer-based multi-label DL model (AnkleNet) was developed and compared with four convolution neural network (CNN) models. Subsequently, a reader study was conducted to evaluate the impact of model assistance on clinicians when diagnosing challenging cases: identifying rotational CAI (RCAI). Diagnostic performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS: Our transformer-based model achieved AUC of 0.910 and 0.892 for detecting lateral and medial collateral ligament injury, respectively, both of which was significantly higher than that of CNN-based models (all P < 0.001). In terms of further CAI diagnosis, it exhibited a macro-average AUC of 0.870 and a balanced accuracy of 0.805. The reader study indicated that incorporation with our model significantly enhanced the diagnostic accuracy of clinicians (P = 0.042), particularly junior clinicians, and led to a reduction in diagnostic variability. The code of the model can be accessed at https://github.com/ChiariRay/AnkleNet. CONCLUSION: Our transformer-based model was able to detect lateral and medial collateral ligament injuries based on MRI and outperformed CNN-based models, demonstrating a promising performance in diagnosing CAI, especially RCAI patients.

A novel allogeneic acellular matrix scaffold for porcine cartilage regeneration.

BACKGROUND: Cartilage defects are common sports injuries without significant treatment. Articular cartilage with inferior regenerative potential resulted in the poor formation of hyaline cartilage in defects. Acellular matrix scaffolds provide a microenvironment and biochemical properties similar to those of native tissues and are widely used for tissue regeneration. Therefore, we aimed to design a novel acellular cartilage matrix scaffold (ACS) for cartilage regeneration and hyaline-like cartilage formation. METHODS: Four types of cartilage injury models, including full-thickness cartilage defects (6.5 and 8.5 mm in diameter and 2.5 mm in depth) and osteochondral defects (6.5 and 8.5 mm in diameter and 5 mm in depth), were constructed in the trochlear groove of the right femurs of pigs (n = 32, female, 25-40 kg). The pigs were divided into 8 groups (4 in each group) based on post-surgery treatment differences. was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and histologic and immunohistochemistry tests. RESULTS: At 6 months, the ACS-implanted group exhibited better defect filling and a greater number of chondrocyte-like cells in the defect area than the blank groups. MRI and micro-CT imaging evaluations revealed that ACS implantation was an effective treatment for cartilage regeneration. The immunohistochemistry results suggested that more hyaline-like cartilage was generated in the defects of the ACS-implanted group. CONCLUSIONS: ACS implantation promoted cartilage repair in full-thickness cartilage defects and osteochondral defects with increased hyaline-like cartilage formation at the 6-month follow-up.

METTL3 promotes SMSCs chondrogenic differentiation by targeting the MMP3, MMP13, and GATA3.

Objective: Synovium-derived mesenchymal stem cells (SMSCs) are multipotential non-hematopoietic progenitor cells that can differentiate into various mesenchymal lineages in adipose and bone tissue, especially in chondrogenesis. Post-transcriptional methylation modifications are relative to the various biological development procedures. N6-methyladenosine (m6A) methylation has been identified as one of the abundant widespread post-transcriptional modifications. However, the connection between the SMSCs differentiation and m6A methylation remains unknown and needs further exploration. Methods: SMSCs were derived from synovial tissues of the knee joint of male Sprague-Dawley (SD) rats. In the chondrogenesis of SMSCs, m6A regulators were detected by quantitative real-time PCR (RT-PCR) and Western blot (WB). We observed the situation that the knockdown of m6A "writer" protein methyltransferase-like (METTL)3 in the chondrogenesis of SMSCs. We also mapped the transcript-wide m6A landscape in chondrogenic differentiation of SMSCs and combined RNA-seq and MeRIP-seq in SMSCs by the interference of METTL3. Results: The expression of m6A regulators were regulated in the chondrogenesis of SMSCs, only METTL3 is the most significant factor. In addition, after the knockdown of METTL3, MeRIP-seq and RNA-seq technology were applied to analyze the transcriptome level in SMSCs. 832 DEGs displayed significant changes, consisting of 438 upregulated genes and 394 downregulated genes. DEGs were enriched in signaling pathways regulating the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and ECM-receptor interaction via Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The findings of this study indicate a difference in transcripts of MMP3, MMP13, and GATA3 containing consensus m6A motifs required for methylation by METTL3. Further, the reduction of METTL3 decreased the expression of MMP3, MMP13, and GATA3. Conclusion: These findings confirm the molecular mechanisms of METTL3-mediated m6A post-transcriptional change in the modulation of SMSCs differentiating into chondrocytes, thus highlighting the potential therapeutic effect of SMSCs for cartilage regeneration.

Arthroscopic Direct Anterior-to-Posterior Suture Suspension Fixation for the Treatment of Posterior Cruciate Ligament Tibial Avulsion Fracture.

OBJECTIVES: A posterior cruciate ligament (PCL) avulsion fracture of the tibial attachment site is a specific type of PCL injury that is difficult and unpleasant to manage. The objective of this study is to report the preliminary results of a newly developed technique: arthroscopic endobutton-suture fixation using a single tibial tunnel. METHODS: From January 2016 to January 2018, 120 patients with PCL avulsion fracture who met our criteria were recruited. Sixty cases were treated by arthroscopic direct anterior-to-posterior suture suspension fixation (endobutton-suture group), and 60 cases were treated by arthroscopic screw-suture fixation (screw-suture group). All radiographic studies were recorded. The curative effect was evaluated by the range of motion (ROM), KT-2000, International Knee Documentation Committee (IKDC) scores, Tegner activity scale, and Lysholm scoring system. For statistical analysis the Student t-test was used. RESULTS: The average follow-up duration was 24 months. Findings and difficulties in surgery are the following. The lax anterior cruciate ligament is one of the diagnostic criteria. The anatomic location of PCL avulsion fractures is deep and surrounded by nerves and vessels; thus, operating through this region is difficult. After each tunnel drilling, the debris at the edge of opening needs to be cleaned to avoid obscuring the operator's vision or wearing the sutures. In endobutton-suture group, ROM improved from 0° preoperatively to 140.0° ± 5.6° at the last follow-up (P < 0.001). The postoperative KT-2000 arthrometric data at 90 N were available for all patients. The IKDC score was 23.6 ± 2.6 and 91.4 ± 4.1 pre- and postoperatively, respectively. The Tegner score improved from 1.2 ± 0.6 to 7.3 ± 2.3 (p < 0.001). The median Lysholm knee score increased from 40.4 ± 5.2 preoperatively to 90.1 ± 10.1 postoperatively (p < 0.001). The operative time was shorter in the endobutton-suture group (p < 0.001). The Lysholm knee score in the endobutton-suture group was lower than that in the endobutton-suture group (3.1 ± 1.2 vs. 4.2 ± 1.8, p < 0.01). No significant complications were noted in the study. CONCLUSIONS: The arthroscopic direct anterior-to-posterior suture suspension fixation is a simple and reliable method that not only provides better clinical outcomes, but also fixes avulsion fragments of any size.

High-Density Lipoprotein Cholesterol and Apolipoprotein A1 in Synovial Fluid: Potential Predictors of Disease Severity of Primary Knee Osteoarthritis.

OBJECTIVES: The aim of this study was to detect levels of common lipid species in serum and synovial fluid (SF) of primary knee osteoarthritis (OA) patients and investigate their correlations with disease severity. MATERIALS AND METHODS: The study enrolled 184 OA patients receiving arthroscopic debridement or total knee arthroplasty and 180 healthy controls between April 2012 and March 2018. Total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were analyzed in serum and SF of OA patients, and in serum of healthy individuals. The Noyes rating criteria, Kellgren-Lawrence (KL) grading system, and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores were, respectively, used to assess cartilage damage, radiographic severity, and symptomatic severity of OA. RESULTS: No significant differences were found in serum TG and ApoB levels between the 2 groups, while OA patients had higher TC and LDL-C levels and lower HDL-C and ApoA1 levels (P < 0.05). Pearson correlation analysis revealed SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage scores, KL grades as well as WOMAC scores (P < 0.05), which were still significant after adjusting for confounding factors (P < 0.05). Receiver operating characteristic curve analysis revealed SF HDL-C (area under the curve [AUC]: 0.816) and ApoA1 (AUC: 0.793) were also good predictors of advanced-stage OA (P < 0.001). CONCLUSION: SF HDL-C and ApoA1 levels were negatively correlated with cartilage damage, radiographic severity, and symptomatic severity of primary knee OA, emerging as potential biomarkers for radiographic advanced-stage OA, which may serve as predictors of disease severity.

Endoscopic reconstruction for chronic Achilles tendon ruptures using a hamstring tendon autograft.

BACKGROUND: To determine the safety and efficacy of endoscopic reconstruction of chronic Achilles tendon ruptures using a hamstring tendon autograft at mid-term follow-up. METHODS: We reviewed the medical records of patients with chronic Achilles tendon rupture treated surgically by endoscopic reconstruction using a hamstring tendon autograft at our institution between March 2010 and October 2015. Radiologic outcomes were assessed using pre- and postoperative magnetic resonance imaging (MRI). Functional outcomes were evaluated with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, the Plantar Flexion Strength (PFS), the Victorian Institute of Sport Assessment-Achilles (VISA-A) scale, the Visual Analogue Scale (VAS) pain score, and the Arner-Lindholm standard. All patients achieved primary healing with no lengthening of the Achilles tendon, skin necrosis, infection, deep vein thrombosis or other complications. RESULTS: Mean follow-up period was 15 ± 3 months (range, 12-18 months). There was no Achilles tendon re-rupture. MRI examination revealed that Achilles tendon continuity was restored. Patients' mean AOFAS, PFS, and VISA-A scores were significantly higher and mean VAS pain score was significantly lower after surgery compared to before (P < 0.05). According to Arner-Lindholm standards, there were twenty (76.9%) excellent, six (23.1%) good, and zero bad outcomes. CONCLUSION: Endoscopic reconstruction utilizing a hamstring tendon autograft is a safe and efficacious option for repair of chronic Achilles tendon ruptures. Studies with larger sample sizes and a longer follow-up are required to confirm the advantage of this technique compared to open surgery.

A modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction: medium-term clinical and radiologic results comparable with open reconstruction.

BACKGROUND: The aim of this study was to compare clinical and radiologic outcomes of a modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction with traditional open reconstruction. METHODS: From January 2012 and March 2016, 60 eligible patients with chronic lateral ankle instability (CLAI) received all arthroscopic remnant-preserving reconstruction or open reconstruction of the anterior talofibular ligament and calcaneofibular ligament using semitendinosus autograft. They were divided into the arthroscopic group (n = 28) and the open group (n = 32). The American Orthopaedic Foot and Ankle Society (AOFAS),visual analog scale (VAS), and Karlsson scores and ankle range of motion (ROM) were used to evaluate clinical outcomes pre-operatively and at six and 12 months and the final follow-up of at least 24 months post-operatively, with SF-36 physical component summary (PCS) and mental component summary (MCS) scores evaluated for quality of life, and the anterior talar translation and talar tilt measurements for radiologic outcomes. RESULTS: There was no difference in pre-operative demographics between two groups (P > 0.05). At the final follow-up, the AOFAS, VAS, Karlsson, SF-36 PCS, and MCS scores improved significantly in both groups (P < 0.05). However, no significant difference was found in AOFAS (91.9 ± 6.8 vs 91.1 ± 5.5), VAS (2.7 ± 1.7 vs 2.5 ± 1.6), Karlsson (95.3 ± 6.7 vs 94.8 ± 6.5), SF-36 PCS (53.2 ± 6.1 vs 52.9 ± 5.7), and MCS scores (55.7 ± 5.8 vs 54.2 ± 5.4) between the two groups (P > 0.05). There was no significant difference in post-operative operated/non-operated ankle ROM between two groups (P > 0.05). No significant difference was observed in talar tilt angle (7.6 ± 4.1° vs 6.8 ± 3.6°) and anterior talar translation (5.8 ± 1.7 mm vs 5.7 ± 1.5 mm) between the two groups at the final follow-up (P > 0.05), although these two variables improved significantly in both groups (P < 0.05). No severe complications were encountered in both groups during the follow-up period. CONCLUSIONS: The modified all-inside arthroscopic remnant-preserving technique of lateral ankle ligament reconstruction could produce excellent clinical and radiologic outcomes comparable with open reconstruction.

Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition).

In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

[Clinical analysis of autogenous tendon reconstruction under total arthroscopy in treatment of chronic Achilles tendon rupture].

OBJECTIVE: To investigate the effectiveness of autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture. METHODS: Between June 2015 and June 2018, 16 patients with chronic Achilles tendon ruptures were treated by autogenous tendon reconstruction under total arthroscopy. Of the 16 patients, 11 were males and 5 were females. Their mean age was 40.7 years (range, 21-55 years). The disease duration was 14-20 months (mean, 16.4 months). Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score was 41.2±2.2 and the pain visual analogue scale (VAS) score was 7.9±1.2. MRI and B-ultrasonography examinations showed that the Achilles tendon was not continuous. The length of Achilles tendon defect was 5.0-10.3 cm, with an average of 5.8 cm. The rupture of the Achilles tendon happened on top of the insertion of the tendon in 4 cases and at the tendon-muscle belly connection in 12 cases. The operation time, intraoperative blood loss, hospital stay, and related complications were recorded. The AOFAS score and VAS score were used to evaluate the improvement of ankle joint function and pain. RESULTS: The average operation time was 77.2 minutes (range, 60-90 minutes). The average intraoperative blood loss was 20.5 mL (range, 15-30 mL). The average hospital stay was 7.2 days (range, 5-10 days). All incisions healed by first intention. There was no skin necrosis, infection, or deep vein thrombosis. All the patients were followed up 8-18 months, with an average of 12 months; and 10 cases were followed up more than 12 months. During the follow-up, there was no Achilles tendon re-rupture, and the symptoms of pain and heel lifting failure significantly improved. MRI reexamination showed that the continuity of Achilles tendon recovered. At 1, 3, 6, and 12 months postoperatively, AOFAS scores significantly improved and VAS scores significantly reduced, except for 1 month postoperatively, the scores at other time points were superior to that before operation, the differences were significant ( P<0.05). CONCLUSION: Autogenous tendon reconstruction under total arthroscopy in the treatment of chronic Achilles tendon rupture has the advantages of small trauma, rapid functional recovery, and satisfactory surgical efficacy.

[Effect of Quantitative indicators of ilium height on approach of percutaneous endoscopic lumbar discectomy treatment in patients with L 5, S 1 lumbar disc herniation].

OBJECTIVE: To identify effect of quantitative indicators of ilium height on approach of percutaneous endoscopic lumbar discectomy (PELD) treatment in patients with L 5, S 1 lumbar disc herniation. METHODS: A retrospective study between May 2014 and March 2016 was conducted, including 100 patients with disc herniation at L 5, S 1, who were initially enrolled for the PELD treatment. Among them, 66 patients were successfully treated with PELD (group A), and the other 34 patients failed to perform puncture, catheterization, or microscopical operation due to the influence of iliac bone and other peripheral bone structures and treated with alternative surgical plans. By analyzing the X-ray films of lumbar vertebrae (including bilateral ilium) of the two groups before operation, the concept of ilium height rate and ilium angle rate was put forward innovatively. The ilium height rate and ilium angle rate of the two groups were measured and compared, and the diagnostic critical points of ilium height rate and ilium angle rate were determined by ROC curve analysis. RESULTS: The ilium height rate was 0.61±0.09, 0.74±0.05 and the ilium angle rate was 0.66±0.08, 0.80±0.08 in groups A and B, respectively, showing significant differences between the two groups ( F=69.729, P=0.000; F=65.165, P=0.000). ROC curve analysis showed that the critical point of ilium height rate was 0.71 (area under ROC curve was 0.927, P=0.000), and the critical point of ilium angle rate was 0.75 (area under ROC curve was 0.965, P=0.000). CONCLUSION: PELD is not recommended for patients with L 5, S 1 intervertebral disc herniation, when the ilium height rate is greater than 0.71 and/or the ilium angle rate is greater than 0.75. Other surgical plans such as transpedicular approach, transpedicular approach, or open surgery, should be recommended to reduce the risk of surgery and the pain of patients.

Relationship of vitamin D receptor gene polymorphisms with susceptibility, surgical outcome and prognosis of hallux valgus in a Chinese Han population.

BACKGROUND: This study aimed to identify the relationship between the vitamin D receptor (VDR) BsmI gene polymorphism and risk factors, surgical outcome and prognosis of hallux valgus (HV). METHODS: A case-control study was performed on a cohort of 236 HV patients and 236 controls in a Chinese Han population. Detection of the VDR BsmI/G2A polymorphism was performed using restriction fragment length polymorphism-polymerase chain reaction. RESULTS: We detected a statistically significant difference in the allele distribution of the BsmI polymorphism between cases and controls (p<0.01). Significant loss of hallux valgus angle (HVA) and intermetatarsal angle (IMA) correction was only noted in patients with the bb genotype during the 2-year follow-up period (p<0.01). The average American Orthopaedic Foot and Ankle Society (AOFAS) scores at the 2-year follow-up were decreased in both groups when compared with those at the 6 month follow-up, and 1.45 points more decrease in patients with the bb genotype was observed as compared to those with the BB and Bb genotypes (p<0.0001). The average visual analogue scales (VAS) also had the tendency with more pains in the bb genotype group (p<0.0001). Furthermore, larger numbers of transfer metatarsalgia were found in patients with the bb genotype upon 2-year follow-up (p=0.049). CONCLUSIONS: We report the first candidate gene polymorphism associated with susceptibility, surgical outcome and prognosis of HV in a Chinese Han population. Moreover, development of genetically-based method to predict the surgical outcome accurately and individualized therapy for HV are warranted.

All arthroscopic remnant-preserving reconstruction of the lateral ligaments of the ankle: A biomechanical study and clinical application.

Lateral ankle sprains are one of the most common injuries in sports. Recently, arthroscopic lateral ligament reconstruction has been recently advocated, however no biomechanical studies and clinical application of this technique are available. In this biomechanical study, eighteen fresh-frozen cadaveric ankles were randomized into three groups: (1) intact anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL), (2) arthroscopic anatomic reconstruction of ATFL and CFL, and (3) all arthroscopic remnant-preserving reconstruction of ATFL and CFL. The specimens were then tested for stiffness and load to ultimate failure using a customized jig. In biomechanical test, the all arthroscopic remnant-preserving reconstruction of ATFL and CFL produced a reconstruction that could withstand loads to failure and stiffness similar to the arthroscopic anatomic reconstruction. However, both two reconstruction groups were much weaker than the intact, uninjured ATFL and CFL. Moreover, we used the technique of all arthroscopic remnant-preserving reconstruction of ATFL and CFL on 20 patients from September 2016 to September 2017. American Orthopaedic Foot and Ankle Society (AOFAS) scores and Anterior Talar Translation (ATT) were applied for statistical collection at preoperative and postoperative 12 months to evaluate clinical efficacy. The differences of the preoperative and postoperative 12 months AOFAS scores and ATT of patients were both statistical significant (P < 0.01). We confirmed that all arthroscopic remnant-preserving reconstruction of ATFL and CFL exhibited positive effect, thus promoting the recovery of ankle function and had good short-term clinical effect.

Association of Vitamin D Receptor Gene TaqI, BsmI, FokI, and ApaI Polymorphisms and Susceptibility to Hallux Valgus in the Chinese Population.

Previous studies have indicated that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with the risk of skeletal malformations with inflammation. However, the potential association of VDR gene polymorphisms with the susceptibility to hallux valgus remains unclear. To clarify this association, we compared the genotypes of 228 patients with hallux valgus with those of 200 controls using the Multiplex SNaPshot system. The χ2 test was used to compare the allele and genotype frequencies between groups, and p ≤ .05 was considered statistically significant. The frequencies of the mutant allele C in TaqI (p= .036; odds ratio [OR] 1.57; 95% confidence interval [CI] 1.03-2.39) and mutant allele A in BsmI (p= .036; OR 1.33; 95% CI 1.02-1.74) were significantly greater in the patients than in the controls. In addition, after adjusting for sex and age, TaqI (p= .047; OR 1.61; 95% CI 1.00-2.58) and BsmI (p= .025; OR 1.67; 95% CI 1.06-2.61) were associated with the risk of hallux valgus through a dominant genetic model. A homozygous genetic model of BsmI was also significantly associated with the risk of hallux valgus (p= .033; OR 1.81; 95% CI 1.05-2.57). However, neither ApaI nor FokI were associated with increased susceptibility. To the best of our knowledge, we have reported for the first time that VDR gene TaqI and BsmI polymorphisms might contribute to the increased risk of hallux valgus in Chinese population.

Comparison of distraction arthroplasty alone versus combined with arthroscopic microfracture in treatment of post-traumatic ankle arthritis.

BACKGROUND: This study aims to compare clinical outcomes of distraction arthroplasty alone versus combined with arthroscopic microfracture in treating post-traumatic ankle arthritis. METHODS: The study cohort consisted of 96 patients (96 ankles) who underwent distraction arthroplasty alone or combined with arthroscopic microfracture between May 2005 and April 2012. Patients were divided into the distraction group (n = 46) and the combined group (n = 50). The American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analog scale (VAS), and ankle activity score (AAS) were used to compare the clinical outcomes between groups. Arthritis severity was assessed on the radiograph. RESULTS: At the mean follow-up period of 30.8 ± 3.1 and 31.4 ± 3.6 months, respectively, no severe complications occurred and no further surgical interventions for symptomatic arthritis were required in both groups. The AOFAS scores improved significantly in the combined group than in the distraction group (59.0 ± 4.7 and 58.0 ± 4.9 preoperatively versus 85.0 ± 4.9 and 88.9 ± 5.4 at final visit, P < 0.001). The AAS scores were also significantly higher in the combined group (3.6 ± 1.1 and 3.3 ± 1.0 preoperatively versus 6.5 ± 1.1 and 7.1 ± 1.3 at final visit, P = 0.009). Pain was significantly alleviated in the combined group by the VAS scores (6.4 ± 0.9 and 6.7 ± 0.9 preoperatively versus 2.3 ± 0.8 and 2.0 ± 0.7 at final visit, P = 0.040). The combined group achieved better radiographic arthritis severity decrease than the distraction group (P = 0.012). CONCLUSIONS: Compared to distraction arthroplasty alone, distraction arthroplasty combined with arthroscopic microfracture can offer better functional recovery, pain relief, and ankle arthritis resolution for treating post-traumatic ankle arthritis.

[Short-term effectiveness of joint distraction by Ilizarov combined with arthroscopic debridement in treatment of knee osteoarthritis].

Objective: To investigate the short-term effectiveness of joint distraction by Ilizarov combined with arthroscopic debridement in the treatment of knee osteoarthritis (KOA). Methods: Between January 2014 and January 2015, 15 patients (15 knees) with KOA were treated using arthroscopic debridement assisting with the Ilizarov distraction technology. There were 7 males and 8 females, aged from 45 to 64 years (mean, 55 years). The left knee and the right knee were involved in 6 and 9 cases respectively. The disease duration was 2.0-9.5 years (median, 6 years). They all had received conservative treatment for 6 months and got poor clinical improvement. The preoperative visual analogue scale (VAS) score, the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, the knee injury and osteoarthritis outcome score (KOOS), the range of motion (ROM) for knee, and the radiographic joint space width were 76.2±8.8, 59.3±5.7, 44.3±7.2, (75±21)°, and (2.5±0.4) mm respectively. According to Kellgren-Lawrence grade system, 11 cases were rated as grade III and 4 cases as grade IV. Results: There was no poor incision healing, infection, and deep vein thrombosis. All the 15 patients were followed up 12-18 months (mean, 15.5 months). Patients achieved pain relief. The knee activity was obviously improved. The postoperative VAS score, WOMAC score, KOOS score, and ROM at 12 months were 20.9±7.8, 38.2±5.5, 92.1±6.9, and (118±14)° respectively, showing significant difference when compared with preoperative ones ( t=18.213, P=0.000; t=10.317, P=0.000; t=18.564, P=0.000; t=6.599, P=0.000). Postoperative X-ray film showed that joint space width at 12 months was (3.8±0.3) mm, showing significant difference when compared with preoperative one ( t=10.070, P=0.000). Conclusion: Joint distraction by Ilizarov combined with arthroscopic debridement can effectively relieve pain, improve the function and quality of life. It was beneficial to cartilaginous tissue repair and delaying the degenerative process of KOA. The short-term effectiveness is satisfactory.

[MODEL ESTABLISHING OF PARTIAL-THICKNESS ARTICULAR CARTILAGE INJURY AND RELATIONSHIPS BETWEEN ACTIVATION OF CELLS AND EXPRESSION OF INTEGRIN ß1IN A RAT MODEL].

OBJECTIVE: To investigate the relationships between the expression of integrin ß1and activated cells in a partial-thickness articular cartilage injury model of adult rats. METHODS: Forty-five male Sprague Dawley rats (aged 10 weeks and weighing 300-400 g) were randomly divided into operated group (n = 15), sham-operated group (n = 15), and control group (n = 15). Partial-thickness articular cartilage injury model was made by scarification in operated group, direct suture after opening of the knee joint was performed in sham-operated group, and no operation was done in control group. Five rats were sacrificed at 1, 7, and 14 days after operation respectively for macroscopic evaluation, HE staining, Safranin O staining, CD105, BrdU, CD105/integrin ß1immunofluorescence and double labeling staining. The histological score of HE staining, gray value of Safranin O staining and CD105-positive cells count were compared among groups at each time point. RESULTS: Macroscopic evaluation showed chondromalacia and cartilage fibrosis around the linear injury with aggravating tendency with time in operated group, but no chondromalacia and cartilage fibrosis in sham-operated and control groups. HE staining demonstrated a number of activated cells accumulating around the linear injury with nonuniform distribution in operated group, and uniform size and distribution in sham-operated and control groups. The histological scores at each time point in operated group were significantly higher than those in sham-operated group and control group (P < 0.05), but no significant difference was found between different time points in 3 groups (P > 0.05). Safranin O staining was nonuniform with hypochromasia around linear injury in operated group, but the staining was uniform in sham-operated group and control group. Gray value of Safranin O staining had no significant difference among groups and among different time points in the same group (P > 0.05). BrdU-positive and CD105-positive cells distributed unevenly around the linear injury in operated group, uniform distribution was observed in sham-operated group and control group. CD105-positive cells count in operated group was significantly higher than those in sham-operated group and control group at each time point (P < 0.05); CD105-positive cells increased significantly with time in operated group (P < 0.05). CD105/integrin ß1-positive cells were observed around the linear injury in operated group, but was not observed in sham-operated group and control group. CONCLUSION: The partial-thickness articular cartilage injury model is successfully established in rats, and cartilage injury could not be repaired completely in the model. The activated cells aggregation around the linear injury can be observed, but there is no obvious relationships between activated cells and cartilage matrix. These activated cells are in proliferation and could express both CD105 and integrin ß1.

Chondrogenic cells respond to partial-thickness defects of articular cartilage in adult rats: an in vivo study.

The purpose of this study was to establish a partial-thickness articular cartilage defects model in adult rats and explore the respond of chondrogenic cells to the cartilage injury. Forty-five adult Sprague-Dawley rats were divided into operated group, sham-operated group and control group. Partial-thickness cartilage defects were created on the weight-bearing region of femoral condyles by a converted ophthalmic knife. Rats were exposed to 5-bromo-2'-deoxyuridine (BrdU) for five consecutive days and were sacrificed 1, 2 and 4 weeks after surgery. Evaluations of macroscopic and histological changes were made. Chondrocyte apoptosis was evaluated by TUNEL assay. Immunofluorescence staining of CD105 and BrdU, double staining of CD105/integrin α5ß1 and CD105-positive cells counting were performed for evaluations of cells around the defects. Cartilage softening and fibrillation with chondrocyte apoptosis were observed around the injury site after surgery. Results of histological scores indicated no significant difference between one time point and a successive time point for either group. CD105-positive cells and BrdU-label-retaining cells were observed around the linear injury. And cells counting showed the number of CD105-positive cells increased at later time points (P < 0.05). Immunofluorescence double staining demonstrated co-localization of CD105 and integrin α5ß1 in activated cells around the defects. We establish a partial-thickness cartilage defects model in adult rats and demonstrate this injury may lead to activation of putative progenitor cells. In addition, the activated cells express integrin α5ß1 specially, which may help in early discovery of osteoarthritis.

[ISOLATION AND IDENTIFICATION OF CARTILAGE PROGENITOR CELLS AND INFLUENCE OF INTERLEUKIN 1ß ON ITS CHONDROGENESIS].

OBJECTIVE: To isolate and identify the cartilage progenitor cells (CPCs) from normal cartilage, and to explore the influence of interleukin 1ß (IL-1ß) in different concentrations on its chondrogenesis. METHODS: CPCs were isolated from normal cartilage of adult New Zealand white rabbit with the fibronectin adhesion assay; the cell phenotype was identified; and the cloning and differentiation of CPCs were observed. CPCs were incubated with H-DMEM in group A, with chondrogenic induced medium in group B, with chondrogenic induced medium+0.1 ng/mL IL-1ß in group C and chondrogenic induced medium+1.0 ng/mL IL-1ß in group D for 3 weeks. The histology, biochemistry, and real-time fluorescence quantitative PCR were performed to observe the effect of IL-1ß on the chondrgenic differentiation. RESULTS: The CPCs from normal cartilage expressed positively stem cell phenotype, which have similar ability of cloning and differentiation to stem cells. The cell pellets in groups C and D were significantly smaller than those in group B, and cell showed hypertrophic morphology change. There were more expressions of collagen type II and collagen type X in group B than in group A, in group B than in groups C and D, and in group C than group D with Safranin O staining. The biochemistry results showed that collagen type II content, glycosaminoglycan (GAG) content, and the ratio of GAG/DNA were significantly lower in groups C and D than in group B (P < 0.05), and in group D than in group C (P < 0.05); but the DNA content was significantly higher in groups C and D than in group B (P < 0.05), and no significant difference between groups C and D (P > 0.05). The real-time fluorescence quantitative PCR results showed that the relative mRNA expressions of collagen type II, collagen type X, and Sox-9 were significantly lower in groups C and D than in group B (P < 0.05), and in group D than in group C (P < 0.05), but the relative mRNA expressions of Runx-2 and matrix metalloproteinase 13 were significantly higher in groups C and D than in group B (P < 0.05), and in group D than in group C (P < 0.05). CONCLUSION: There are CPCs having the character of stem cells in normal cartilage, and they have the capability of cloning and potential differentiation. IL-1ß can inhibit the chondrogenesis of CPCs, and possibly promote the osteogenic differentiation.

Microfracture combined with osteochondral paste implantation was more effective than microfracture alone for full-thickness cartilage repair.

PURPOSE: The aim of this study was to evaluate whether the microfracture combined with osteochondral paste implantation could promote the quality of the regenerated tissue in the knee joints of rabbits. METHODS: Sixty-six New Zealand white rabbits were used. Bilateral knee joints from the same rabbit were randomly divided into experimental group and microfracture group. An articular cartilage defect was established in the femoral trochlear groove. In the experimental group, the defect was microfractured and covered with osteochondral paste harvested from the intercondylar notch. The regenerated tissues were harvested for gross morphology, histology, biochemistry and gene expression analysis at 4, 8 and 12 weeks postoperatively. RESULTS: The regenerated tissue had a slowly mature process in both groups. At 12 weeks, the regenerated tissue in the experimental group appeared much more thicker and white with higher percentages of defect filling macroscopically. In histology, the experimental group found a majority of hyaline-like regenerate tissue with intense Safranin-O and collagen type II staining, while fibrocartilage-like tissue was mostly seen in the microfracture group with poor Safranin-O and collagen type II staining. The experimental group had higher Wakitani scores and narrower acellular zones than those in the microfracture group (P < 0.05). For biochemical analysis, both the GAG content and the DNA-normalized GAG content saw a time-dependent increase with a much higher value found in the experimental group at 8 and 12 weeks (P < 0.05). On the contrary, the total DNA content decreased with time in both groups, and the difference between the two groups was only found at 4 and 8 weeks (P < 0.05). For gene expression analysis, the experimental group had much higher expression levels than the microfracture group as for collagen type II and aggrecan, but not for collagen type I. CONCLUSION: Microfracture combined with paste implantation can result in improved quality of the reparative tissue and may have a positive effect on the integration to the surrounding cartilage in the rabbit model. The technique offers a promising treatment option for cartilage defects and improves the regeneration of articular cartilage for patients with painful chondral lesions.

[Correlation between expression of aquaporins 1 and chondrocyte apoptosis in articular chondrocyte of osteoarthritis].

OBJECTIVE: The changes of the aquaporins 1 (AQP-1) expression may be related to the chondrocyte apoptosis. To explore the correlation between the expression of AQP-1 and chondrocyte apoptosis by observing the expression of the AQP-1 and the Caspase-3, so as to provide experimental evidence for the further study in the pathogenesis of osteoarthritis (OA). METHODS: Seventy-two 8-week-old clean grade male Sprague Dawley rats, weighing 286-320 g (mean, 300 g), were randomly divided into the operated group (n = 24), the sham-operated group (n = 24), and the control group (n = 24). OA models were made by amputating the anterior cruciate ligament and medial collateral ligament, and partial excision of medial meniscus in operated group; the articular cavity was exposed only in sham-operated group; and no treatment was given in control group. The general condition of the rat was observed after model was established. At 1, 2, 4, and 8 weeks, the specimens of knee joints were harvested to perform the gross and histological observations; the mRNA expressions of AQP-1 and Caspase-3 were determined by real-time fluorescent quantitative PCR; and the activity of the Caspase-3 protease was detected. The correlations between the expression of AQP-1 mRNA and the expressions of Caspase-3 mRNA and protease were analyzed. RESULTS: Totally 6 rats died after operation, and the rats were supplied immediately; the other rats survived to the end of experiment. The appearance and structure of knee articular cartilage were normal in control group and sham-operated group. While in operated group, the cartilage had a rough surface with fissure and vegetation, and fibrosis and irregular cell arrangement were seen on the surface of cartilage. There were significant differences in the Mankin score between the operated group and sham-operated group, control group at 2, 4, and 8 weeks (P < 0.05). There was no significant difference in expressions of the AQP-1 mRNA and Caspase-3 mRNA, and the activity of the Caspase-3 protease among 3 groups at 1 week after operation (P > 0.05); while the expressions of the AQP-1 mRNA, Caspase-3 mRNA, and the activity of the Caspase-3 protease in operated group were significantly higher than those in sham-operated group and control group at 2, 4, and 8 weeks after operation (P < 0.05), and there was an increased trend over time. There was significantly positive correlation (r = 0.817, P = 0.000) between the expressions of AQP-1 mRNA and Caspase-3 mRNA, and the regression equation was y = 0.426 7x(2) + 0.051 5x; meanwhile, there was also significantly positive correlation (r = 0.945, P = 0.000) between the expression of AQP-1 mRNA and the activity of Caspase-3 protease, and the regression equation was y = 15.423 0x + 4.392 8. CONCLUSION: The up-regulation of AQP-1 expression in OA cartilage may be related to the chondrocyte apoptosis, and the changes of AQP-1 expression may involve in the pathogenesis of OA.